1. Field of the Invention
This invention is generally related to the measurement of concentrations of elements, compounds or other analytes in a fluid or in a gaseous mixture, and more specifically, to the measurement of concentrations of oxygen in a fluid or in a gaseous mixture.
2. Description of the Related Art
A number of methods and apparatus have been developed to measure concentrations of an analyte such as elements or compounds in a fluid or a gaseous mixture. These measurement methods and apparatus have become particularly important in modern medicine, where blood chemistry and other life-critical diagnostic and monitoring measurements have become increasingly important to the sophisticated treatments available. Among such measurement methods and apparatus have been those directed to the measurement of the concentration of oxygen in the blood based upon the phenomenon of quenching of the emissions from certain dyes which are used as indicators. Systems incorporating these methods have been incorporated into intravascular catheters which are used to measure concentrations of oxygen in the blood. In such catheters, optical fibers are used to conduct excitation light generated in an external instrument to the sensing element incorporating the indicator at the distal tip of the catheter and to transmit the resulting emitted light from the sensing element back to the detection system of the external instrument.
While such measurement methods have been shown to be quite useful and have acceptable sensitivity and accuracy, the indicated oxygen concentration often tends to drift or otherwise show inaccuracies or biases, since the intensity of the fluorescence is a function of a number of factors related to the apparatus and dye in addition to the oxygen concentration. These factors include the power of the excitation light, transmission of the optical fiber, the temperature of the sample, the concentration of the indicator dye, and the local environment of the indicator (e.g., changes in the dye-matrix conformation when the dye is immobilized in an analyte permeable matrix). It has been widely recognized that optical sensors show greatly enhanced performance and/or stability when the system includes a means for referencing the intensity of the output to a stable independent source. Ideally, the intensity of this second source should illustrate the same variation in intensity from factors that influence the oxygen sensitive component, with the exception of the oxygen sensitivity. In that case, the quotient of the two fluorescences will yield a ratio which is dependent only upon the concentration of oxygen.
A variety of different approaches have been proposed to provide such reference means, including providing a sample of the indicator which is not exposed to the oxygen, the use of a separate indicator compound or the use of a different chemical form of the indicator. All of these approaches result in a more complex apparatus that may not necessarily provide compensation for a variety of allied indicator degradation phenomena, such as differential photobleaching or differential leaching of the indicator and reference compounds from the sensing element. While it has been suggested that a single chemical compound can be used as both as an indicator and a reference material o the basis of ratioing the fluorescence and phosphorescence of that compound, the reagents developed for such use have not been suitable for the analysis of aqueous and other liquid samples and such a method has been shown to be of limited utility.
There remains, therefore, a need for a means of referencing the output of indicators which employ the phenomenon of fluorescent quenching which is simple and easily implemented in catheter systems and which provides a means of accurate normalization within a wide variation in the fluorescent emission of the indicator. Furthermore, it would be extremely helpful if such a method could be applied to a variety of indicators and does not require additional complex electronics or optics associated with the excitation and measurement scheme.